16 December 2009

There was a very interesting article published in the 05 November 2009 issue of Science magazine on the composition of bacterial colonies in humans. A human has more bacterial cells living in and on it than it does have human cells. Costello et al. (2009) (also see Supplemental Online Material which I think is free access and comprises 90 % of the article) took bacterial samples from 7-9 humans (likely the authors' themselves) over several months to assess both the composition of bacterial colonies from various sites such as the gut, forehead, and nostril, and to assess whether the composition changed with time. They found significant variation from person to person but not a lot of change over time. Hence the notion that we all have our own individual bacterial flora.

Bacteria on the surface of the various membranes that separate our innards from our environment are essentially the first line of defense against intruders. They form more or less continuous biofilms consisting of bacteria held together by a matrix of congealing substance, such as mucous. Bacteria colonies on our bodies are mostly symbiotic, although they can be parasitic at which point they become pathogens. So there are 'good' and 'bad' bacteria. What determines whether we have mostly 'good' symbiotic bacteria or not? How do we encourage the development of 'good' bacterial flora and discourage harmful flora? Good bacteria can out-compete pathogens, predigest anti-nutrients before they can penetrate the gut lining, thereby providing useful symbiotic services to us.

These are questions I do not have answers to, but I do have hypotheses.

Bacteria are prokaryotes, which means they are much much smaller and simpler than any one of our cells in our body. In fact they are about the same size as the mitochondria organelles in our cells. Mitochondria are the ATP-producing energy factories of our cells, and all they do is break apart fatty acids (called beta-oxidation) and oxidize Acetyl-CoA, the produce of beta-oxidation and glycolysis of glucose. A bacterium has to to all that and more all in a small package. As a result, bacteria often can only exist on certain nutrients: lactose, glucose, fatty-acids with a certain number of carbons, etc. These are called metabolic pathways, and they represent a specific set of chemical reactions that eventually result in the production of ATP, the energy currency of living things.

The obvious conclusion to draw here is that macronutrient ratios will likely be fairly important for determining the composition of gut flora, but it will not be a question of carbohydrate versus fat. It will be a question of 4-chain saturated fatty acids versus 18-chain monounsaturates, glucose versus fructose versus galactose, because that's the level of detail required for metabolic pathways. In addition, there is almost certain to be some synergy between various forms of bacteria when they form little symbiotic colonies, with one living off the metabolic produces of the other.

Micronutrients may also matter to gut biofilm composition. Most biochemical processes in the body require enzymes to catalyze the reaction. Enzymes are usually protein chains in which one amino acid group has had a elemental substitution that acts as an active site with chemical activity. An example is the iron site on hemoglobin that binds oxygen in your red blood cells. I would guess that bacteria can do the substitution themselves, which is to say they should be able to build their own enzymes from the elemental forms of the required minerals rather than necessarily requiring the amino group preformed. The point I am trying to make is mineral deficiencies might kill off various strains of gut bacteria.

Overall I think this line of research is very interesting and likely to provide many interesting results. This might, for example, end up being a very strong argument against the prophylactic employment of antibiotics. At a minimum, patients should be prescribed probiotic cultures after their antibiotic treatments, and, oh yeah, those probiotics should actually be, you know, alive when ingested.

A useful research project would be a large-scale longitudinal study (tens of thousands of patients over 10 - 15 years), where patients' gut bacterial colonies are sampled at regular intervals and the patients are monitored for the development of various diseases. The initial states of gut flora, if they remain consistent, may produce correlations for the relative risks of various diseases. If the composition changes, the natural question is if any new diseases presented at the same time. The US National Institute for Health has instituted a survey program to determine the genomes of gut flora, the Human Microbiome Program, which is an important first step.

I started taking a Lactobacillus and Bifidobacterium probiotic a couple of weeks ago as a trial. I did notice changes in my stool almost immediately; for the sake of brevity I will spare you the details. Bacterial cultures, like fish oil, should be stored in the refrigerator but unlike fish oil bacteria don't withstand freezing too well.